This invention relates to peripheral benzodiazepines.
Based on their predominant receptor binding affinity, benzodiazepines (BZDs) have been grouped into two pharmacologically distinct subclasses: central and peripheral.
Most of the clinically potent benzodiazepines, such as diazepam, oxazepam and clonazepam, have a strong binding affinity to the central BZD receptor, but very weak binding affinity to the peripheral BZD (pBZD) receptor. Central-type receptors are located in the brain and are believed to be involved in the therapeutic action of the central acting BZDs.
Peripheral BZD receptors, on the other hand, are widely distributed in many tissues and cell types including kidney, lung, heart, adrenal cortex, platelets, mast cells, lymphocytes and brain and may be involved in the regulation of cell proliferation and growth. Peripheral benzodiaze pines exhibit "in vivo" immunosuppressive properties by inhibiting the capacity of macrophage to produce lymphokines such as IL-1, IL-6 and TNF (Zavala et al., The J. of Pharmacology and Experimental Therapeutics, 255, 442, 1990). (Johnson, et al., J. Pharmacol. Exp. Therap. 238, 855-859, 1986; Morgan, et al., Proc. Natl. Acad. Sci. U.S.A., 82, 5223-5226, 1985; Solowey, et al., J. Interferon Res. 10, 269-280, 1990 and Cancer Lett., 49, 115, 1990.